The regulation of enzyme levels in immature and neoplastic rat tissues is the broad purpose of this investigation. In brain, the normal organ to be studied most thoroughly, we shall quantify through fetal and postnatal life the amounts of 10-12 enzymes, determine their subcellular distribution and identify physiological stimuli which trigger their synthesis. We shall describe the interference of high phenylalanine blood levels (maintained artificially during the first three postnatal weeks) with cerebral biochemical differentiation. Enzyme inductions in transplantable lymphosarcoma, well-differentiated renal and hepatic tumors will be compared with the cognate adult and normal immature tissue. Alterations in growth rate and enzymic composition of tumors, when transplanted into neonates or after treatment with substances found to regulate enzymic differentiation in normal fetal tissues, will be determined. Suckling rats will be used to show the extent to which transplanted tumors and treatment with chemical carcinogens interfere with normal enzymic differentiation of liver, kidney and brain. Explants of fetal and neonatal liver will be employed to study in vitro the mechanisms of selective gene expression as enhanced by hormones or rendered abnormal by the presence of carcinogens in the culture medium.